Abstract

In recent decades, the incidence of invasive fungal infections has increased notably. Candida albicans (C. albicans), a common opportunistic fungal pathogen that dwells on human mucosal surfaces, can cause fungal infections, especially in immunocompromised and high-risk surgical patients. In addition, the wide use of antifungal agents has likely contributed to resistance of C. albicans to traditional antifungal drugs, increasing the difficulty of treatment. Thus, it is urgent to identify novel antifungal drugs to cope with C. albicans infections. Heat shock proteins (Hsps) exist in most organisms and are expressed in response to thermal stress. In C. albicans, Hsps control basic physiological activities or virulence via interaction with a variety of diverse regulators of cellular signaling pathways. Moreover, it has been demonstrated that Hsps confer drug resistance to C. albicans. Many studies have shown that disrupting the normal functions of C. albicans Hsps inhibits fungal growth or reverses the tolerance of C. albicans to traditional antifungal drugs. Here, we review known functions of the diverse Hsp family, Hsp-associated intracellular signaling pathways and potential antifungal targets based on these pathways in C. albicans. We hope this review will aid in revealing potential new roles of C. albicans Hsps in addition to canonical heat stress adaptions and provide more insight into identifying potential novel antifungal targets.

Highlights

  • C. albicans causes superficial and potentially life-threatening systemic infections, especially in immunocompromised and high-risk surgical patients (Dimopoulos et al, 2007)

  • Further studies suggest that in addition to regulating thermal adaptations, Heat shock proteins (Hsps) act as molecular chaperones that interact with many molecules in diverse signaling pathways, such as the calcium-calcineurin signaling pathway, MAP kinase (MAPK) signaling pathways, the Ras1-cAMPPKA signaling pathway and cell cycle control pathways

  • These Hsp-associated pathways are essential for controlling basic physiological activities and virulence of C. albicans

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Summary

INTRODUCTION

C. albicans causes superficial and potentially life-threatening systemic infections, especially in immunocompromised and high-risk surgical patients (Dimopoulos et al, 2007). Many studies demonstrate that Hsp plays an important role in thermal stability, morphogensis, cell cycle regulation, apoptosis, and drug resistance in C. albicans (Leach et al, 2012b; O’meara and Cowen, 2014). HSP990 was shown to exhibit low cytotoxicity in human umbilical vein endothelial cells (Li et al, 2015) This finding is a promising prospect for the clinical application of non-GdA Hsp inhibitors to treat C. albicans infections. Has hindered the development of Hsp inhibitors for clinical application, it is promising to find drugs with low cytotoxicity, like HSP990, and there is future potential to find specific targets of C. albicans Hsp90 Another way to inhibit Hsp is via stimulation of the host immune response (Bugli et al, 2013).

Methods and results
CONCLUSION
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